Theranostics 2013-01-01

Sequential systemic administrations of combretastatin A4 Phosphate and radioiodinated hypericin exert synergistic targeted theranostic effects with prolonged survival on SCID mice carrying bifocal tumor xenografts.

Junjie Li, Marlein Miranda Cona, Feng Chen, Yuanbo Feng, Lin Zhou, Guozhi Zhang, Johan Nuyts, Peter de Witte, Jian Zhang, Jie Yu, Raymond Oyen, Alfons Verbruggen, Yicheng Ni

Index: Theranostics 3(2) , 127-37, (2013)

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Abstract

Based on the soil-to-seeds principle, we explored the small-molecular sequential dual-targeting theranostic strategy (SMSDTTS) for prolonged survival and imaging detectability in a xenograft tumor model.Thirty severe combined immunodeficiency (SCID) mice bearing bilateral radiation-induced fibrosarcoma-1 (RIF-1) subcutaneously were divided into group A of SMSDTTS with sequential intravenous injections of combretastatin A4 phosphate (CA4P) and (131)I-iodohypericin ((131)I-Hyp) at a 24 h interval; group B of single targeting control with CA4P and vehicle of (131)I-Hyp; and group C of vehicle control (10 mice per group). Tumoricidal events were monitored by in vivo magnetic resonance imaging (MRI) and planar gamma scintiscan, and validated by ex vivo autoradiography and histopathology. Besides, 9 mice received sequential intravenous injections of CA4P and (131)I-Hyp were subjected to biodistribution analysis at 24, 72 and 120 h.Gamma counting revealed fast clearance of (131)I-Hyp from normal organs but intense accumulation in necrotic tumor over 120 h. After only one treatment, significantly prolonged survival (p<0.001) was found in group A compared to group B and C with median survival of 33, 22, and 21 days respectively. Tumor volume on day 15 was 2.0 ± 0.89, 5.66 ± 1.66, and 5.02 ± 1.0 cm(3) with tumor doubling time 7.8 ± 2.8, 4.4 ± 0.67, and 4.5 ± 0.5 days respectively. SMSDTTS treated tumors were visualized as hot spots on gamma scintiscans, and necrosis over tumor ratio remained consistently high on MRI, autoradiography and histology.The synergistic antitumor effects, multifocal targetability, simultaneous theranostic property, and good tolerance of the SMSDTTS were evident in this experiment, which warrants further development for preclinical and clinical applications.